•The gas production from hydrate dissociation accounting for about 85%.•Analysis of the radius of the hydrate dissociation area in this production test.•Five-year prediction of long-term influence ...radius of pressure drop.•Exploration of favorable areas for the formation of secondary hydrates.•Analysis of the response of pressure and temperature of hydrate reservoirs.
The first offshore natural gas hydrate production test of China in 2017 has proved the feasibility of hydrate exploitation from clayey-silt reservoirs, which possesses the highest reservoirs than other types of hydrate resources. However, owing to the absence of monitoring wells in this production test, the hydrate dissociation behavior cannot be analyzed through pressure and temperature changes of hydrate reservoirs. This paper focuses on the simulation study on the detailed response of the temperature and pore pressure of hydrate reservoirs of Well SHSC-4 during the gas production by depressurization. Meanwhile, it highlights the analysis of favorable areas for the formation of secondary hydrates and the influence of the secondary hydrates on pressure and temperature field of hydrate reservoirs. The simulation results indicate that in the first 60 days, the hydrate reservoirs feature a dissociation radius of about 5 m, and the gas production from hydrate dissociation accounts for about 85%. After 1 year, 2 years and 5 years of hydrate exploitation, the influence radius of low-pressure area (<10 MPa) is 15 m, 16 m and 17 m, respectively, suggesting that the hydrate reservoirs have higher gas production efficiency in the first year. Furthermore, the temperature and pressure of hydrate reservoirs are not favorable to the formation of secondary hydrates in the first 60 days. In long-term production, secondary hydrates are mainly formed at hydrate dissociation front. This can increase the pore pressure and further decrease the effective stress in the local areas of hydrate reservoirs, thus affecting mechanical stability of the local hydrate reservoirs.
Numerous studies have determined that physical cues, especially the nanotopography of materials, play key roles in directing stem cell differentiation. However, most research on nanoarrays for stem ...cell fate regulation is based on nonbiodegradable materials, such as silicon wafers, TiO2, and poly(methyl methacrylate), which are rarely used as tissue engineering biomaterials. In this study, we prepared biodegradable polylactic acid (PLA) nanopillar arrays with different diameters but the same center-to-center distance using a series of anodic aluminum oxide nanowell arrays as templates. Human adipose-derived stem cells (hADSCs) were selected to investigate the effect of the diameter of PLA nanopillar arrays on stem cell differentiation. By culturing hADSCs without the assistance of any growth factors or osteogenic-induced media, the differentiation tendencies of hADSCs on the nanopillar arrays were assessed at the gene and protein levels. The assessment results suggested that the osteogenic differentiation of hADSCs can be driven by nanopillar arrays, especially by nanopillar arrays with a diameter of 200 nm. Moreover, an in vivo animal model of the samples demonstrated that PLA film with the 200 nm pillar array exhibits an improved ectopic osteogenic ability compared with the planar PLA film after 4 weeks of ectopic implantation. This study has provided a new variable to investigate in the interaction between stem cells and nanoarray structures, which will guide the bone regeneration clinical research field. This work paves the way for the utility of degradable biopolymer nanoarrays with specific geometrical and mechanical signals in biomedical applications, such as patches and strips for spine fusion, bone crack repair, and restoration of tooth enamel.
Nanostructured hydroxyapatite (HAp) has been applied widely as a scaffold material for bone tissue engineering for its good osteoinduction and biodegradability. However, the degradation process and ...the distribution of degraded HAp within the bone-defect cavity is still not clear. To visually study the behavior of HAp in bone repair process, a membrane of HAp/terbium (Tb)-HAp nanowires (NWs) was prepared with a concentric circle structure (CCS), of which the inner circle and the outer ring were constructed with Tb-HAp and HAp NWs, respectively. HAp/Tb-HAp CCS membrane possessed good osteogenic capacity and efficient fluorescence in the center for visualization. The in vitro experimental results proved that the Tb-HAp and HAp NWs membranes both presented high cytocompatibility and adequate efficiency to induce osteogenic differentiation of bone marrow stem cells (BMSCs). HAp/Tb-HAp CCS membranes were then implanted into a rat calvarial bone-defect model to study the behavior of HAp in bone repair process in vivo by tracking the fluorescence distribution. The results showed that the fluorescence of Tb-HAp diffused gradually from the inner circle to the outer ring, which suggested that the HAp was first degraded, and then the degraded product was diffused and finally reconstructed. Further, the histological results proved that the doping of Tb did not impair the promotive effect of HAp on bone repair process. Therefore, this study provided a visual method to observe the degradation-diffusion-reconstruction behavior of HAp nanomaterials in bone repair process.
The study of dynamic degradation process of implanted hydroxyapatite (HAp) materials in bone-defect cavity is of great significance to bone tissue engineering applications. Here, we designed a HAp/Tb-HAp nanowires (NWs) membrane with concentric circle structure (CCS) to visibly observe the behavior of HAp during bone repair process. HAp/Tb-HAp CCS membrane possessed both osteoinduction ability and fluorescence property. Calvarial bone-defect repair experiments in vivo showed that the fluorescence of Tb-HAp diffused gradually from inner circle to outer ring, which suggested that HAp was first degraded, then diffused and finally reconstructed. Therefore, this invention provides not only a visible method to observe the degradation-diffusion-reconstruction behavior of HAp-based biomaterials, but also a basic understanding of the dynamic change of HAp-based biomaterials.
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The precise functions and mechanisms of microRNAs (miR) in gallbladder cancer (GBC) remain elusive. In this study, we found that miR‐135a‐5p expression is often dampened and correlated with neoplasm ...histologic grade in GBC. MicroRNA‐135a‐5p introduction clearly inhibited GBC cell proliferation in vitro and in vivo. Moreover, very low density lipoprotein receptor (VLDLR), which is often upregulated in GBC tissues, was identified as a direct functional target of miR‐135a‐5p. Furthermore, the p38 MAPK pathway was proven to be involved in miR‐135a‐VLDLR downstream signaling. Together, these results suggested that the miR‐135a–VLDLR–p38 axis may contribute to GBC cell proliferation.
In this study, we reported that miR‐135a is often upregulated in GBC tissues and associated with the neoplasm histologic grade for the first time. Ectopic mir‐135a expression could inhibit the proliferation of GBC cells in vitro and in vivo. Moreover, we identified that VLDLR is a direct target of miR‐135a, and p38 MAPK pathway contributes to the inhibitory effect of miR‐135a on GBC cells.
Proinflammatory (M1) macrophages play a vital role in antitumor immunity, and regulation of proinflammatory macrophage polarization is critical for immunotherapy. The polarization of macrophages can ...be regulated by biological or chemical stimulation, but investigations of the regulatory effect of physical stimulation are limited. Herein, regulating macrophage polarization with localized electrical signals derived from a piezoelectric β‐phase poly(vinylidene fluoride) (β‐PVDF) film in a wireless mode is proposed. Charges released on the surface of the β‐PVDF film driven by ultrasonic irradiation can significantly enhance the M1 polarization of macrophages. Mechanistic investigation confirms that electrical potentials rather than reactive oxygen species and mechanical forces enable Ca2+ influx through voltage‐gated channels and establishment of the Ca2+‐CAMK2A‐NF‐κB axis to promote the proinflammatory macrophage response during ultrasound treatment. Piezoelectric material‐mediated electrical signal‐activated proinflammatory macrophages significantly inhibit tumor cell proliferation. A method for electrogenetic regulation of immune cells as well as a powerful tool for engineering macrophages for immunotherapy is provided here.
Regulating macrophage polarization with localized electrical signals derived from a piezoelectric β‐phase poly(vinylidene fluoride) (β‐PVDF) film in a wireless mode is proposed, providing a method for electrogenetic regulation of immune cells as well as a powerful tool for engineering macrophages for immunotherapy.
The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration. Although various cytokines or chemokines have been widely applied in periodontal in situ ...tissue engineering, most of them are macromolecular proteins with the drawbacks of short effective half-life, poor stability and high cost, which constrain their clinical translation. Our study aimed to develop a difunctional structure for periodontal tissue regeneration by incorporating an angiogenic small molecule, dimethyloxalylglycine (DMOG), and an osteoinductive inorganic nanomaterial, nanosilicate (nSi) into poly (lactic-co-glycolic acid) (PLGA) fibers by electrospinning. The physiochemical properties of DMOG/nSi-PLGA fibrous membranes were characterized. Thereafter, the effect of DMOG/nSi-PLGA membranes on periodontal tissue regeneration was evaluated by detecting osteogenic and angiogenic differentiation potential of periodontal ligament stem cells (PDLSCs) in vitro. Additionally, the fibrous membranes were transplanted into rat periodontal defects, and tissue regeneration was assessed with histological evaluation, micro-computed tomography (micro-CT), and immunohistochemical analysis. DMOG/nSi-PLGA membranes possessed preferable mechanical property and biocompatibility. PDLSCs seeded on the DMOG/nSi-PLGA membranes showed up-regulated expression of osteogenic and angiogenic markers, higher alkaline phosphatase (ALP) activity, and more tube formation in comparison with single application. Further, in vivo study showed that the DMOG/nSi-PLGA membranes promoted recruitment of CD90+/CD34− stromal cells, induced angiogenesis and osteogenesis, and regenerated cementum-ligament-bone complex in periodontal defects. Consequently, the combination of DMOG and nSi exerted admirable effects on periodontal tissue regeneration. DMOG/nSi-PLGA fibrous membranes could enhance and orchestrate osteogenesis-angiogenesis, and may have the potential to be translated as an effective scaffold in periodontal tissue engineering.
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•Dual-load fibrous structure possessed preferable mechanical property and biocompatibility.•Fibrous structure can orchestrate and enhance osteogenesis-angiogenesis coupling.•Difunctional fibrous structure can recruit CD90+/CD34− stromal cells to periodontal defects.•Difunctional fibrous structure obtained functional periodontal tissue regeneration.
Osteoimmunomodulation was identified as a new and important strategy to enhance osteogenic differentiation together with other osteogenic approaches. However, approaches regulating osteogenic ...differentiation and macrophage polarization to remodel an osteoinductive microenvironment are separate and complicated. Therefore, the design and synthesis of one biomaterial that couples the osteogenic performance and immunomodulatory ability is a major challenge for efficient bone repair. In this study, self-assembled iron-catechin nanoparticles (Fe-cat NPs) were designed based on the coordinated reaction between iron ions and catechin and synthesized via a facile one-pot strategy. Interestingly, Fe-cat NPs show intracellular pH-responsive disassembly and release catechin molecules under the low pH of lysosomes after endocytosis. This strategy delivers catechin intracellularly and then enhances the osteogenic differentiation while inhibits the adipogenic differentiation of human adipose-derived stem cells (hADSCs). More importantly, Fe-cat NPs remodel the osteogenic immune microenvironment by resisting inflammation and promoting M2 polarization of macrophages. As a promising metal-organic nanodrug, the intracellular pH-responsive Fe-cat NPs significantly enhance the therapeutic effect of bone regneration by orchestrating osteogenic differentiation and immunomodulation, which may have great potential in bone tissue engineering.
Immediate and effective hemostatic treatments for complex bleeding wounds are an urgent clinical demand. Hemostatic materials with characteristics of adhesion, sealing, anti‐infection, and ...concrescence promotion have drawn growing concerns. However, pure natural multifunctional hemostatic materials with in situ ultrafast self‐gelation are rarely reported. In this study, a hydro‐sensitive collagen/tannic acid (ColTA) natural hemostatic powder is developed that can in situ self‐gel to form adhesive by the non‐covalent crosslinking between tannic acid (TA) and collagen (Col) in liquids. The physical interactions endow ColTA adhesive with the characteristics of instantaneous formation and high adhesion at various substrate surfaces. Crucially, ColTA powder adhesive shows an enhanced adhesion performance in the presence of blood due to the electrostatic interactions between ColTA adhesive and red blood cells, conducive to effective in situ sealing and rapid hemostasis. The biocompatible and hemocompatible ColTA adhesive can effectively control bleeding and seal the wounds of the caudal vein, liver, heart, and femoral arteries in rats. Furthermore, the low‐cost and ready‐to‐use ColTA adhesive powder also possesses good antibacterial and inhibiting biofilm formation ability, and can efficiently regulate immune response by the NF‐κB pathway to promote wound repair, making it a highly promising hemostatic material with great potential for biomedical applications.
A hydro‐sensitive collagen/tannic acid (ColTA) natural hemostatic powder that can in situ self‐gel to form adhesive by the non‐covalent crosslinking. ColTA powder adhesive shows a red blood cell‐enhanced adhesion performance to effectively control bleeding and seal the wounds and possesses good antibacterial and inhibiting biofilm formation ability, and immune regulation by the NF‐κB pathway to promote wound repair.
We study the collision frequencies of charged particles in the complex plasmas with the two-parameter and three-parameter non-Maxwellian velocity distributions. The average collision frequencies of ...electron–ion, electron–electron and ion–ion for the distributions are derived, respectively. We show that the average collision frequencies in the complex plasmas depend strongly on the parameters in the non-Maxwellian distributions and thus are significantly different from those cases in the plasmas with a Maxwell velocity distribution. The significant effects of the non-Maxwell parameters on the average collision frequencies are numerically analyzed. The results have important impacts on the transport coefficients and transport properties of charged particles in the highly or fully ionized complex plasmas.
Ever‐growing tissue regeneration and other stem cell therapies cause pressing need for large population of self‐renewable stem cells. However, stem cells gradually lose their stemness after long‐term ...in vitro cultivation. In this study, a ZnO nanorod (ZnO NR) array is used to maintain the stemness of human adipose‐derived stem cells (hADSCs). The results prove that after culturing hADSCs on ZnO NRs for 3 weeks, the stemness genes and protein expression level are higher than that on culture plates and ZnO film. ZnO NRs can maintain stemness of hADSCs without inhibiting the cell proliferation and oriented differentiation capabilities. KLF4 (Kruppel‐like factor 4) is a Zn2+‐binding gene that plays a vital role in cell proliferation and differentiation. Sustained Zn2+ release and the increased expression of KLF4 can be detected, suggesting that ZnO NRs have efficiently released Zn2+ for stemness maintenance. Taken together, the nanotopography of ZnO NRs and the Zn2+ release synergistically facilitate stemness maintenance. This study has provided a powerful tool for directing cell fate, maintaining stemness, and realizing the expansion of stem cells in vitro, which will open a new route for the manufacture of large populations of stem cells and fulfilling the growing demand for the cell therapy market.
In this study, ZnO nanorods (ZnO NRs) are fabricated as a scaffold for long‐term effective stemness maintenance of human adipose‐derived stem cells (hADSCs). After culturing hADSCs on ZnO NRs, their self‐renewal ability and differentiation potential can be retained. This study has provided a powerful tool for directing cell fate, maintaining stemness, and realizing the expansion of stem cells in vitro.
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